MiR-146a在类风湿关节炎外周血单个核细胞中的表达及意义
ltered Expression of MiR-146a in Periphery Blood Mononuclear Cells of Rheumatoid Arthritis
目的:了解类风湿关节炎(RA)患者外周血单个核细胞(PBMC)中差异表达的miRNAs,探讨RA患者PBMC中miR-146a表达与RA的相关性,以及可能的调控机制。方法:1、提取RA患者及正常对照各5例PBMC总RNA。通过微阵列芯片技术分析miRNAs表达谱。2、在芯片检测结果基础上,选择与免疫调节功能密切相关的miR-146a,利用实时定量聚合酶链方法(Real-time PCR, RT-PCR)测定RA患者及正常对照者各31例PBMC中miR-146a的表达水平。3、评价miR-146a的表达水平与RA患者临床及实验室指标的相关性。4、利用RT-PCR测定miR-146a靶标TRAF6 、IRAK1的表达水平,分析其与miR-146a表达水平的相关性。结果:1、miRNAs微阵列芯片表达谱提示RA患者PBMC中有46种miRNAs异常表达,其中miR-146a低表达。2、miR-146a的表达与血沉(ESR)的水平呈正相关。 3、miR-146a的表达与其靶标TRAF6 、IRAK1成负相关。结论:RA患者PBMC中miR-146a 表达水平下降, 可能通过其靶标TRAF6 、IRAK1参与I 型干扰素通路正调控作用, 从而参与疾病的发生发展。
Objectives: To investigate the expression level of miR-146a in PBMCs of RA and its possible regulatory mechanism. Methods: Expression profiling of miRNAs was performed in a microarray analysis. The down-regulated miR-146a in RA was identified for further study including 31 patients of RA and 31 normal controls by real-time PCR. Associations between miR-146a and the clinical and laboratory features of RA were evaluated. The target mRNAs of miR-146a: TRAF6 and IRAK1 levels were detected by real-time PCR. Results: 1. Expression profiling of miRNAs revealed significant differential expression of 46 miRNAs. MiR-146a was much lower in PBMCs of RA than normal controls. 2. Expression level of miR-146a was negatively associated with ESR. 3. Expression levels of miR-146a were significantly decreased in patients with moderate or severe disease activity compared to normal controls. 3. The level of miR-146a was negatively correlated with that of its target mRNAs: IRAK1 and TRAF6. Conclusions: MiR-146a may be a negative indicator of RA disease activity and a down-regulator in RA pathogenesis by serving as a regulator of type I IFN signaling via posttranscriptional regulation of expression of the IRAK1 and TRAF6 proteins.
史晋霞、李茹、龙丽、栗占国
基础医学内科学
miR-146a外周血单个核细胞类风湿关节炎
miR-146aperiphery blood mononuclear cellsrheumatoid arthritis
史晋霞,李茹,龙丽,栗占国.MiR-146a在类风湿关节炎外周血单个核细胞中的表达及意义[EB/OL].(2011-12-16)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201112-463.点此复制
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